The Skok Lab investigates how 3D genome architecture—shaped by CTCF/CTCFL, cohesin, transcription factors, and nucleosomes—controls gene expression in development and is rewired in cancer. We pair mechanism-driven biology with tools we build: fixed 3D DNA/RNA FISH and dual-colour live-cell CRISPR imaging; EpiMethylTag and MethNet; and cluster-based single-molecule nano-NOMe phasing with molecule stitching that connect CTCF states, nucleosome positioning, and long-range contacts to transcription. Our foundational lymphocyte work first demonstrated chromatin looping and locus contraction in individual nuclei, explaining antigen-receptor diversity and informing current studies of insulated-domain reprogramming and damage-imprinted chromatin memory.